The functional significance of aromatase and other androgen transformations in CNS target tissues may be to regulate synthesis of biologically active versus inactive hormone and thereby to control hormone uptake and binding quantitatively and qualitatively region by region within the CNS. In addition, metabolism may be one mechanism for determining target tissue sensitivity to circulating steroid. If so, one would expect to find changes in enzyme activity in specific brain regions under natural and artificial conditions when steroid feedback and behavioral responsiveness are known to vary. The proposed studies are designed to test this hypothesis in hamsters. The enzymes of major interest are aromatase, 5 alpha- and 5 beta-reductase. Using 3H-substrate in a quantitative assay for tissue homogenates, we plan to: (1) determine the quantitative distribution of these enzymes in microdissected hypothalamic and limbic structures and devise a standardized dissection procedure for all subsequent experiments; (2) measure activity in brain of male and female hamsters from birth to sexual maturity with attention to the critical period of brain sex differentiation and the onset of puberty; (3) compare activity in brain of adult females on each of the 4 days of the estrous cycle; (4) compare activity in brain of adult males at monthly intervals for one year while maintained under natural photoperiod and temperature; (5) measure activity in brain of males and females in relation to daily light-dark cycles; (6) record possible responses in brain enzyme activity after experimental manipulation of feedback sensitivity in castrated male hamsters by short daily photoperiods; (7) in selected experimental groups, compare results of in vitro assay with metabolite composition of whole tissues and purified cell nuclei following a peripheral injection of 3H-substrate. If it is true that steroid metabolic enzymes at the level of brain target tissues are a fine-tuning mechanism controlling feedback and behavioral responses, a new approach to the diagnosis and treatment of neurendocrine dysfunction and artificial control of fertility will be feasible.